Serum albumin is the major vehicle for the transport of free fatty acids released from adipose tissue and the ability of albumin to bind long chain fatty acids is essential to normal lipid metabolism. Albumin from patients with atherosclerosis has been observed to have a lower binding capacity for fatty acids than does albumin from non-atherosclerotic patients or healthy volunteers. No reason for this difference has been proposed inasmuch as relatively little information is available on the specific binding sites for fatty acids on albumin in terms of their locations, amino acid content or three-dimensional nature. In this investigation it is proposed to locate and characterize fatty acid binding regions of human albumin. Fatty acid binding sites of albumin will be modified through affinity labeling with activated enol esters of radioactive long chain fatty acids. Samples of labeled albumin will be cleaved by chemical or enzymatic means to produce various small peptide fragments. Fragments will be isolated by chromatographic procedures and characterized by amino acid composition and sequence. Peptide segments which carry label will be assumed to have originated from a fatty acid binding site on albumin and their identification will identify the residues of albumin contributing to fatty acid binding sites. The distribution of fatty acid binding sites within the albumin molecule and the fatty acid content and binding capacity of the isolated albumin samples will be compared for atherosclerotic and non-atherosclerotic populations.